The polymerase chain reaction has been adapted from Barnes' protocol for long PCR to incorporate a high level of an exonuclease-free, N-terminal deletion mutant of Taq DNA polymerase in combination with a very low level of a thermostable DNA polymerase exhibiting a 3' exonuclease activity. The reaction was modified to include a reverse-transcription step and was optimized for use with hepatitis C virus genomes as template. It has been possible to amplify large amounts of 4 to 4.8 kb of hepatitis C virus genome from clinical samples. This amplified cDNA will be sequenced to complete genotyping studies of the virus, and used for the construction of full-length, possibly infectious, cDNA molecules.